JAMDA 16 (2015) 296e300

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Original Study

Depression, Frailty, and All-Cause Mortality: A Cohort Study of Men Older than 75 Years Osvaldo P. Almeida MD, PhD a, b, c, *, Graeme J. Hankey MD d, e, Bu B. Yeap MBBS, PhD e, f, Jonathan Golledge MChir g, h, Paul E. Norman DS i, Leon Flicker MBBS, PhD b, d, j a

School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia WA Center for Health and Aging, Center for Medical Research, Perth, Australia c Department of Psychiatry, Royal Perth Hospital, Perth, Australia d School of Medicine and Pharmacology, University of Western Australia, Perth, Australia e Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia f Department of Endocrinology, Fremantle and Fiona Stanley Hospital, Perth, Australia g Queensland Research Center for Peripheral Vascular Disease, School of, Medicine and Dentistry, James Cook University, Townsville, Australia h Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Australia i School of Surgery, University of Western Australia, Perth, Australia j Department of Geriatric Medicine, Royal Perth Hospital, Perth, Australia b

a b s t r a c t Keywords: Depression mortality frailty cohort study elderly

Background: Depression is associated with increased mortality, but it is unclear if this relationship is truly causal. Objectives: To determine the relative mortality associated with past and current depression, taking into account the effect of frailty. Design, Setting, and Participants: Prospective longitudinal cohort study of 2565 men aged 75 years or over living in metropolitan Perth, Western Australia, who completed the third wave of assessments of the Health In Men Study throughout 2008. Main Outcome and Measures: All-cause mortality data were derived from Australian death records up to June 17, 2013. History of past depression and age of onset of symptoms were obtained from direct questioning and from electronic health record linkage. Diagnosis of current major depressive symptoms followed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision guidelines. We considered that participants were frail if they showed evidence of impairment in 3 or more of the 5 domains on the fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale. Other measured factors included age, education, living arrangements, smoking and alcohol history, and physical activity. Results: 558 participants died during mean period of follow-up of 4.2  1.1 years. The annual death rate per thousand was 50 for men without depression, 52 for men with past depression, and 201 for men with major depressive symptoms at baseline. The crude mortality hazard was 4.26 (95% confidence interval ¼ 2.98, 6.09) for men with depression at baseline compared with never depressed men, and 1.79 (95% confidence interval ¼ 1.21, 2.62) after adjustment for frailty. Further decline in mortality hazard was observed after adjustment for other measured factors. Conclusions: Current, but not past, depression is associated with increased mortality, and this excess mortality is strongly associated with frailty. Interventions designed to decrease depression-related mortality in later life may need to focus on ameliorating frailty in addition to treating depression. Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

This work was funded through competitive project grants from the National Health and Medical Research Council of Australia (NHMRC), numbers 279408, 379600, 403963, 513823, and 634492. The authors declare no conflicts of interest. http://dx.doi.org/10.1016/j.jamda.2014.10.023 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

* Address correspondence to Osvaldo P. Almeida, MD, PhD, School of Psychiatry and Clinical Neurosciences (M573), University of Western Australia, 35 Stirling Highway, Crawley, Perth, WA 6009, Australia. E-mail address: [email protected] (O.P. Almeida).

O.P. Almeida et al. / JAMDA 16 (2015) 296e300

Depression is a common mental disorder that affects about 10% of those older than 60 years of age.1,2 People with depression are subject to deteriorating quality of life, as well as to increased disability, morbidity, and mortality compared with their nondepressed peers.3e5 The mechanisms linking depression to negative health outcomes such as death are not clear, but unhealthy lifestyle practices, high disease burden, and decreased heart rate variability may all play a part.6e8 There is also some evidence, albeit inconclusive, that the risk of death increases with the severity of the depressive episode.9,10 Antidepressants are effective at reducing the severity of symptoms11 but seem to have an equivocal impact on long-term mortality, particularly later in life.12,13 There are 3 possible ways of explaining this observation. First, depression (or its treatment) could be associated with damaging physiological changes that extend beyond those involved in the expression of depressive signs and symptoms, and those changes might fail to normalize with antidepressant treatment. For example, depression is associated with decreased heart rate variability, but effective antidepressant treatment does not reverse these changes.13 Second, older adults with depression include a group of people with recurrent or chronic depressive episodes, and this could lead to a pattern of repetitive exposure to stress and deteriorating health.14,15 In this case, the increased risk of death associated with depression could be due to the presence of recurrent rather than simply the current depressive episode. Finally, it is conceivable that the excess mortality associated with depression in later life is due to the presence of comorbid physical illnesses that trigger both depressive symptoms and a cascade of events that ultimately result in death.16 If depression increases mortality, one might expect older people exposed to depression earlier in life to have greater absolute risk of death than late onset cases, as the former would have been exposed for longer to the conceivably damaging physiological changes associated with depression. Alternatively, if depression later in life is a marker of frailty, current rather than past depression would be associated with increased risk of death. Clarifying this issue is important because if longstanding history of depression increases mortality, then developing effective secondary preventive strategies should be highlighted as research and public health priorities. Conversely, if depression in late life is a marker of frailty, death might only be successfully delayed if the factors that contribute to increasing frailty can be identified and ameliorated. We designed this study to determine the mortality associated with remote and recent past depression, as well as with current depression, in a cohort of community-dwelling men older than 75 years. The null hypotheses of the study were that the mortality hazard of men with past (recent or remote), and current depression would be similar to that of men who had never been depressed before study entry. Methods Study Design and Setting This was a prospective cohort study of community-dwelling men living in the Perth metropolitan region, Western Australia. Participants This investigation included 2565 men aged 75 years or over who took part in the third wave of assessments of the Health In Men Study (HIMS) throughout 2008. HIMS is an ongoing longitudinal study of a community-representative sample of 12,203 men aged 65e84 years recruited via the Australian Electoral roll during 1996e1998.17 In order to take part in HIMS, participants had to be willing to complete a structured health questionnaire and to undergo an ultrasound for

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abdominal aortic aneurysm. During 2001e2004, 5485 survivors were invited to complete a second wave of assessments. The third wave took place in 2008. The Human Research Ethics Committees of the University of Western Australia and of the Department of Health of Western Australia approved the study protocol, which followed the principles of the Declaration of Helsinki. All men provided written informed consent to participate. Outcome of Interest The outcome of interest in this study was death by any cause (specific causes of death were not available). We used the Western Australian Data Linkage System (WADLS) to retrieve information from death records across Australia, including the date of death. WADLS connects death and multiple health records, including all acute hospital admissions, hospital movements, cancer, and mental health registries for residents of Western Australia.18,19 Data were censored on June 18, 2013. Explanatory Variables Current and past depression were the exposures of interest in this study. We used the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms during wave 3 of HIMS.20 To meet criteria for a current depressive episode, participants had to indicate that they had experienced ‘little pleasure in doing things’ and/or had been ‘feeling down, depressed or hopeless’ for a week or more during the previous 2 weeks. In addition, men had to report experiencing at least 5 of the 9 symptoms described in the PHQ-9 for most days during the same 2week period: (1) decreased interest or pleasure; (2) low mood; (3) sleep disturbance; (4) lack of energy; (5) disturbed appetite; (6) feelings of failure or guilt; (7) poor concentration; (8) psychomotor disturbance; and (9) suicidal thoughts. Men who fulfilled both requirements and indicated that these problems made working, taking care of things at home, or getting along with other people ‘somewhat difficult’ or ‘extremely difficult,’ received the diagnosis of a current major depressive episode. In addition, during the third wave of assessments for HIMS, we asked participants if a doctor had ever told them that they had had a depressive episode (yes/no) and, for those who responded in the affirmative, we asked them to indicate how old they were at the time they were ‘first told’ they had depression. We used this information to indicate history of past depression and approximate age of onset of symptoms. We also used data retrieved from WADLS to ascertain the history of health contacts associated with diagnosis of a depressive episode according to International Classification of Diseases, Ninth Revision codes 296.2, 296.3, 296.82, 296.90, 298.0, and 311, and International Classification of Diseases Tenth Revision codes F32, F33, F34.1, and F38.10. We used these data to estimate the age at the time of first contact. The final age of onset of depression represented the youngest age from either self-report or WADLS. We then subtracted the age of onset of depression from the age of participants at the time of assessment at HIMS wave 3 to calculate the duration of the depressive disorder and classified the history of depression as nonexistent (never depressed), remote (>5 years), recent (5 years), or current. Other study measures included age (in years), high school education (completed or not), marital status, living arrangements (alone or with others), smoking (never, past or current), and alcohol history (never or occasional,

Depression, frailty, and all-cause mortality: a cohort study of men older than 75 years.

Depression is associated with increased mortality, but it is unclear if this relationship is truly causal...
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